Ultrawide-field fluorescein angiography features in patients with anterior uveitis.

PURPOSE: To evaluate the utility of ultrawide-field fluorescein angiography (UWFFA) in patients with anterior uveitis by investigating the detection of retinal vascular leakage (RVL) and the subsequent implications on disease diagnosis and management. STUDY DESIGN/MATERIALS AND METHODS: Patients, who were referred to the National Eye Institute (NEI) for evaluation of anterior uveitis and underwent UWFFA imaging at the initial visit, were included in this study. The electronic medical records of eligible patients were reviewed. The UWFFA images were assessed for severity of retinal vascular leakage, presence of macular leakage, and optic disc leakage by a two-grader system, and intergrader agreement was calculated using the κ-value. Patients with altered diagnoses and management attributable to UWFFA results were noted. RESULTS: A total of 93 eyes of 63 patients were included in the study. Of 93 eyes, 31 (33.3%) eyes had RVL on UWFFA, with 26 (28.0%) eyes and 5 (5.4%) eyes showing mild and moderate-severe RVL, respectively. Twenty-five (26.9%) eyes showed macular leakage, and 7 (7.5%) eyes showed optic disc leakage. The κ-values ranged from 0.85 - 0.87 indicating excellent intergrader agreement. Of the 31 eyes with RVL, the diagnosis was changed to anterior/intermediate uveitis for 9 (29.0%) eyes and to panuveitis for 4 (12.9%) eyes. Systemic treatment was escalated in 5 patients. CONCLUSION: Our results suggest that UWFFA imaging is useful in detecting subclinical posterior involvement in patients with anterior uveitis. Moreover, UWFFA results in altered diagnosis and treatment approaches in a portion of patients.

Choroidal amelanotic mass with vermiform margins, vision loss, and extreme fatigue.

PURPOSE: To describe a case of a previously healthy middle-aged male with an atypical choroidal mass and fatigue. METHODS: Case report. RESULTS: A 56-year-old Caucasian male presented with decreased vision in the right eye (OD) and a choroidal amelanotic mass OD with subretinal fluid. He received bevacizumab (1.25 mg/0.05 mL) injections by multiple providers without improvement in vision and with tumor progression. Visual acuity was 20/400 OD and 20/25 left eye (OS). The anterior segment was unremarkable in both eyes (OU). He was referred with suspected diagnosis of choroidal melanoma, metastasis, or osteoma. On examination, a choroidal amelanotic tumor with vermiform margins measuring 12 mm in base and 1.8 mm in thickness was seen OD. Smaller satellite lesions were noted inferiorly. Fundus OS was normal. Infectious evaluation was unrevealing and angiotensin-converting enzyme, lysozyme, and chest x-ray were normal. Fine-needle aspiration biopsy was declined by the patient. Given the clinical suspicion of choroidal sarcoidosis with characteristic tumor color, vermiform margins, and presence of satellite lesions, oral corticosteroids 60 mg/day for 2 months were started, followed by sub-Tenons triamcinolone acetonide (40mg/1 mL) injection three months later and urgent rheumatologic evaluation. He self-discontinued the oral corticosteroids and the tumor progressed by the next follow-up. Oral corticosteroids were restarted at 80mg/day. 16 months after his presentation to us, he experienced fatigue with electrocardiogram findings of third-degree heart block from sarcoidosis. He received an intracardiac defibrillator and 80 mg/day of corticosteroids with plans to initiate methotrexate for stronger immunosuppression. CONCLUSION: Understanding the numerous manifestations of ocular and systemic sarcoidosis is crucial. Choroidal sarcoidosis characteristically exhibits vermiform margins. Close follow-up and systemic monitoring is necessary in patients presenting with ocular signs of sarcoidosis. PRECIS: The diagnosis of choroidal sarcoidosis can be challenging. Features including vermiform tumor margins, satellite lesions, and choroidal infiltration on OCT are suggestive of choroidal sarcoidosis. All patients with ocular sarcoidosis should be monitored for systemic involvement. In this case, the ocular manifestation guided the diagnosis and eventually the treatment of cardiac sarcoidosis.

Bilateral Exudative Retinal Detachments and Panuveitis in a Patient with Multiple Myeloma.

PURPOSE: To report a case of bilateral exudative retinal detachments and panuveitis in a patient with multiple myeloma (MM). CASE REPORT: A 54-year-old patient with non-proliferative diabetic retinopathy was referred with blurred vision and scotomas in both eyes (OU). Three months prior to the onset of ocular symptoms, he was diagnosed with systemic MM and was receiving chemotherapy. Clinical examination revealed best-corrected visual acuities of 20/80 OU, rare anterior chamber cell, 2+ vitreous cell, diffuse intraretinal hemorrhages, and exudative retinal detachments (RD). Optical coherence tomography of the macula showed central subretinal fluid with cystic intraretinal fluid OU. The findings were consistent with panuveitis and exudative RD in the setting of MM. He reported symptomatic improvement after plasmapheresis and oral prednisone initiation. CONCLUSION: Extensive, bilateral exudative RD and panuveitis are rare but potentially sight-threatening findings in patients with MM.

Birt-Hogg-Dubé syndrome associated with chorioretinopathy and nyctalopia: a case report and review of the literature.

PURPOSE: To report a rare case of Birt-Hogg-Dubé Syndrome (BHD) with progressive chorioretinopathy. METHODS: Case report. RESULTS: A 55-year-old woman presented with longstanding nyctalopia attributed to a congenital retinal dystrophy, but no prior genetic testing. Her posterior pole examination demonstrated retinal pigment epithelium (RPE) mottling with extensive macular drusen and paracentral chorioretinal atrophy, consistent with a fleck retinopathy. Her past medical history was remarkable for nephrectomy for unilateral renal malignancy, parotid tumors and thyroid nodules. Dark adaptation time was prolonged, and electroretinography (ERG) revealed abnormal waveforms with depressed amplitudes. Genetic testing confirmed a deletion mutation in the folliculin (FLCN) gene and was negative for other relevant mutations, including EFEMP1 responsible for autosomal dominant macular and peripapillary drusen in Doyne honeycomb retinal dystrophy and TIMP3 responsible for Sorsby Fundus Dystrophy. CONCLUSION: BHD is a rare autosomal-dominant disorder with multi-systemic clinical manifestations caused by a mutation in the FLCN gene. Affected individuals are prone to renal and pulmonary cysts, renal cancer, and fibrofolliculomas. Reports on ocular manifestations of BHD include eyelid fibrofolliculomas, flecked chorioretinopathy, choroidal melanoma, choroidal melanoma with sector melanocytosis, and retinal pigment epithelial micro-detachments. In this case of BHD, we note a fleck retinopathy with bilateral chorioretinal atrophy, displaying a phenotype of extensive chorioretinopathy associated with impaired dark adaptation and ERG abnormalities. ABBREVIATIONS: BHD: Birt-Hogg-Dubé syndrome; FLCN: Folliculin. RPE: retinal pigment epithelium; OD: Oculus dexter (right eye); OS: Oculus sinister (left eye). OU: Oculus uterque (both eyes); ERG: electroretinogram; mfERG: multifocal electroretinography. ffERG: full-field electroretinography; FAF: fundus autofluorescence; OCT: optical coherence tomography; FA: fluorescein angiography; DA: dark-adapted; LA: light-adapted; mTOR: mammalian target of rapamycin; EFEMP1: epithelial growth factor-containing fibulin-like extracellular matrix protein 1; VPS13B: Vacuolar Protein Sorting 13 Homolog B; AGBL5: AATP/GTP-Binding Protein Like 5; ALMS1: Alstrom Syndrome 1; COL1BA1: Collagen Type I Beta, Alpha Chain 1; PDE6A: Rod Phosphodiesterase 6-alpha; USH2A: Usherin 2a; VCAN: Versican; RP: Retinitis pigmentosa; AR: Autosomal recessive.

Education on Vaccination Competence: an Intensive Course for Skillful Health Science Students.

Background: Vaccination is one of the most successful and cost-effective interventions for public health. Studies have shown that health professionals who have good knowledge and positive attitudes towards vaccination are more likely to provide effective vaccination protection to people, including themselves. Therefore, health science students must acquire evidence-based knowledge during their education to meet the challenges of healthcare. Objective: The aim of this study was to investigate the knowledge, attitudes and feedback of health science students who participated in the Educating Vaccination Competence (EDUVAC) Intensive Course. Methods: A five-day Intensive Course was implemented for health science students, which included a pre-assignment. The EDUVAC Intensive Course used different teaching methods (lectures, workshops, interactive games, discussions), group work, study visits, and cultural programs to encourage students' motivation. For the purpose of the study, students filled out an online questionnaire after giving informed consent. Results: Sample consisted of 31 health science students from five European Higher Institutions. They had very good knowledge on most knowledge questions. In the post measurement it was significantly greater and equal to 81%, p<0.001. Almost all students (93.5%) totally agreed that "It is important for adults to receive all recommended vaccines according to national guidelines". The statement "I have had an active attitude and participation in the Intensive Course" received 80.6% total agreement. Over 90.3% rated the Intensive Course as "excellent" or "above average". Conclusions: After completing the EDUVAC Intensive Course, students felt confident in their vaccination knowledge and skills, which benefited their professional development.

Assessment of Retinal Changes Following Intravitreal Aflibercept in 2 Patients With Von Hippel-Lindau Disease-Related Retinal Capillary Hemangioblastoma.

This case report of 2 patients describes peripheral Von Hippel-Lindau disease associated with a series of aflibercept injections.

Targeting the YAP/TAZ Pathway in Uveal and Conjunctival Melanoma With Verteporfin.

Purpose: The purpose of this study was to determine whether YAP/TAZ activation in uveal melanoma (UM) and the susceptibility of melanoma cell lines to YAP/TAZ inhibition by verteporfin (VP) is related to the tumor's genetic background. Methods: Characteristics of 144 patients with enucleated UM were analyzed together with mRNA expression levels of YAP/TAZ-related genes (80 patients from the The Cancer Genome Atlas [TCGA] project and 64 patients from Leiden, The Netherlands). VP was administered to cell lines 92.1, OMM1, Mel270, XMP46, and MM28 (UM), CRMM1 and CRMM2 (conjunctival melanoma), and OCM3 (cutaneous melanoma). Viability, growth speed, and expression of YAP1-related proteins were assessed. Results: In TCGA data, high expression of YAP1 and WWTR1 correlated with the presence of monosomy 3 (P = 0.009 and P < 0.001, respectively) and BAP1-loss (P = 0.003 and P = 0.001, respectively) in the primary UM; metastasis development correlated with higher expression of YAP1 (P = 0.05) and WWTR1 (P = 0.003). In Leiden data, downstream transcription factor TEAD4 was increased in cases with M3/BAP1-loss (P = 0.002 and P = 0.006) and related to metastasis (P = 0.004). UM cell lines 92.1, OMM1, and Mel270 (GNAQ/11-mutation, BAP1-positive) and the fast-growing cell line OCM3 (BRAF-mutation) showed decreased proliferation after exposure to VP. Two slow-growing UM cell lines XMP46 and MM28 (GNAQ/11-mutation, BAP1-negative) were not sensitive to VP, and neither were the two conjunctival melanoma cell lines (BRAF/NRAS-mutation). Conclusions: High risk UM showed an increased expression of YAP/TAZ-related genes. Although most UM cell lines responded in vitro to VP, BAP1-negative and conjunctival melanoma cell lines did not. Not only the mutational background, but also cell growth rate is an important predictor of response to YAP/TAZ inhibition by VP.

Retinal Imaging Using a Confocal Scanning Laser Ophthalmoscope-Based High-Magnification Module.

PURPOSE: To evaluate the usefulness of a high-magnification module (HMM) lens to visualize retinal photoreceptors, retinal nerve fiber layer (RNFL), and superficial retinal vasculature in physiologic and pathologic retinal conditions. DESIGN: Observational descriptive study. PARTICIPANTS: Thirty-two participants with normal and pathologic retina examination results. METHODS: Normal and pathologic maculae were imaged in vivo using still and video HMM lens modes, with fixation and contrast adjustments to enhance visualization. The HMM images were classified qualitatively based on structures identified as either good (photoreceptors seen), average (photoreceptor mosaic cannot be visualized clearly, retinal vessels and other retinal changes can be seen), or poor (no identifiable structures). Selected eyes were imaged with fundus photography, OCT, OCT angiography, indocyanine green angiography, and fluorescein angiography for comparison with the pathologic maculae. MAIN OUTCOMES MEASURES: Description of HMM module-obtained macula images. RESULTS: From 32 eyes imaged (16 normal and 16 pathologic retinas), 12 of 16 normal and 11 of 16 pathologic retinas demonstrated at least average image quality, in which retinal vasculature and landmarks could be visualized. The mosaic pattern of hexagonal shapes representing photoreceptors could not be resolved in most pathologic retinas. For the retinas in which the photoreceptor mosaics were visualized (12 of 16 normal and 2 of 16 pathologic retinas), parafoveal mosaic patterns appeared denser with better image quality for all participants compared with foveal photoreceptors. Difficulty in resolving the photoreceptors in the umbo, fovea, and perifovea was encountered, similar to what has been reported with adaptive optics devices. The RNFL was seen as arcuate hyperreflective bundles. Flow was observed in the macular microvasculature. Poorly resolved photoreceptors and scattered hyperreflective foci were correlated with changes in the retinal pigment epithelium in eyes with age-related macular degeneration or central serous chorioretinopathy. Macular striae were seen in eyes with epiretinal membrane. CONCLUSIONS: In most eyes, regardless of whether retinal pathologic features were present, it was challenging to obtain average quality (or better) images. In the few participants with good-quality imaging, the parafoveal photoreceptor mosaic, vascular flow, and various features of pathologic eyes could be visualized.

The association between adherence to the Mediterranean diet and childhood obesity; the role of family structure: Results from an epidemiological study in 1728 Greek students.

BACKGROUND: Childhood obesity is among the leading public health challenges, worldwide. AIM: To examine the association between children's adherence to the Mediterranean diet (MD) and weight status taking into account family structure and related behaviors. METHODS: 1728 primary-school Greek students (46% males), from Athens metropolitan area, island of Crete, and the Peloponnese region, were enroled during school years 2014-2016. Children and their parents completed questionnaires which, among others, recorded family structure (i.e., married/cohabited, divorced, single parent, and widowed), dietary and lifestyle habits. Adherence to the MD was assessed through the KIDMED score (range - 4 to 12). Children's body mass index was calculated and classified as normal, overweight/obese, according to the International Obesity Task Force classification. The working sample was 1142 children (44% males) with a recorded family structure. RESULTS: The prevalence of overweight was 21.7% and obesity was 5.0%; overweight/obesity prevalence was higher among males than females (32.4% vs. 23.3%; p < 0.001). Overweight/obese children had a lower KIDMED score compared to normal weight (median (range): 4 (-2, 11) vs. 5 (-1, 10), p = 0.05). An inverse association between KIDMED score and children's weight status (odds ratio (OR) (95% confidence interval (CI)): 0.95 (0.89-0.99)) was observed. Interaction between family structure and KIDMED was observed (p < 0.001); stratified analysis revealed that in children from nuclear families the KIDMED score was inversely associated with the likelihood of overweight/obesity (OR (95% CI): 0.95 (0.88-1.00)), whereas in children from single-parent families it was not (OR (95% CI): 0.94 (0.79-1.12)). CONCLUSION: Adherence to the MD plays a protective role against childhood overweight/obesity, particularly among children living in nuclear families.

Acadesine suppresses TNF-α induced complement component 3 (C3), in retinal pigment epithelial (RPE) cells.

RATIONALE: Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness in the developed world. Aging, inflammation and complement dysregulation affecting the retinal pigment epithelium (RPE), are considered significant contributors in its pathogenesis and several evidences have linked tumor necrosis factor alpha (TNF-α) and complement component 3 (C3) with AMD. Acadesine, an analog of AMP and an AMP-activated protein kinase (AMPK) activator, has been shown to have cytoprotective effects in human clinical trials as well as having anti-inflammatory and anti-vascular exudative effects in animals. The purpose of this study was to evaluate if acadesine is able to suppress TNF-α induced C3 in RPE cells. METHODS: ARPE-19 and human primary RPE cells were cultured and allowed to grow to confluence. TNF-α was used for C3 induction in the presence or absence of acadesine. Small molecule inhibitors and siRNA were used to determine if acadesine exerts its effect via the extracellular or intracellular pathway and to evaluate the importance of AMPK for these effects. The expression level of C3 was determined by immunoblot analysis. RESULTS: Acadesine suppresses TNF-α induced C3 in a dose dependent manner. When we utilized the adenosine receptor inhibitor dipyridamole (DPY) along with acadesine, acadesine's effects were abolished, indicating the necessity of acadesine to enter the cell in order to exert it's action. However, pretreatment with 5-iodotubericidin (5-Iodo), an adenosine kinase (AK) inhibitor, didn't prevent acadesine from decreasing TNF-α induced C3 expression suggesting that acadesine does not exert its effect through AMP conversion and subsequent activation of AMPK. Consistent with this, knockdown of AMPK α catalytic subunit did not affect the inhibitory effect of acadesine on TNF-α upregulation of C3. CONCLUSIONS: Our results suggest that acadesine suppresses TNF-α induced C3, likely through an AMPK-independent pathway, and could have potential use in complement over activation diseases.

Online Education for Vaccination Competence Among Health Sciences Students.

The EDUVAC project aims to develop and implement a web-based course on educating vaccination competence among health sciences students. In the current study students' feedback and evaluation is assessed which guided the partners' efforts to improve the final course content and learning material that will be available for open access. After completing the web-based course, most of the students (N=103, 75.1%) perceived their vaccination knowledge was up to date and their overall participating experience was "above average or excellent (N=119, 86.9%). While, almost all of the students (N=127, 92.7%) found that the web-based course has benefitted them and their future career. Our findings support that the web-based courses can provide satisfactory learning experience to University students and offer flexibility when needed especially in times that remote education is the only option.